The sterilization of surgical supplies and parenteral drugs is a carefully controlled process. An effective commonly used method of sterilization is by the use of steam under pressure. However, many surgical instruments and supplies are adversely affected by heat, and sterilization at high temperature is not practical for those items.
An outgrowth of agricultural and industrial fumigation is gaseous sterilization using ethylene oxide as the sterilant. The advantages of gaseous sterilization are: sterilization is at low temperatures thus avoiding damage to heat and moisture-sensitive materials, objects or items can be terminally sterilized in their packages and the equipment required is simple.
The parameters which affect sterilization processes using ethylene oxide are exposure time, gas concentration, temperature and humidity. When diluted ethylene oxide is added relative humidities below about 30% RH limit the effectiveness of the process. High humidities, e.g., above 90%, also result in inadequate processing. The time required for sterilization is inversely proportional to gas concentration and decreases with increasing temperature. Hence, a useful process control must be sensitive to humidity, temperature, gas concentration and the processing time elapsed.
The gas concentration generally used is about 450 mg/lt to about 1,500 mg/lt while processing temperature may vary from about 70.degree. F to about 140.degree. F.
In order to achieve sterilization processing times may vary from about 45 minutes to several hours. Of course, humidity must be in the proper range to effectively sterilize, e.g., 40-80% R.H.
The classical method for determining the effectiveness of any microbial sterilization process is to include in the system exposed to the sterilizing process a suitable resistant organism. For ethylene oxide sterilization the organisms used are the spores of Bacillus subtilis var. niger. These spores exhibit high resistance to ethylene oxide. Such a method suffers from the fact that at least several days are required to culture the spores in order to verify the effectiveness of the sterilization process. Additionally, the spores, being living organisms, the rate at which they are killed is a logarithmic relationship with time, resulting in a broad time window between initial and complete spore kill.
In the field of heat sterilization various physical indicators have been developed to monitor the sterilization process. These vary in quality from the simplest, melt indicators which merely show that a particular temperature has been achieved to a sophisticated device which responds to time, temperature and steam known as Thermolog .RTM. S, see for example U.S. Pat. No. 3,946,611.
Various physical monitors have been developed in an attempt to monitor ethylene oxide sterilization. 4(4-Nitrobenzyl)pyridine has been used as an indicator when applied to a paper strip; see for example Journal of Pharmaceutical Sciences, Brewer et al., pages 57-59, January 1966. Other compounds including pyridines and quinolines have also been used; see U.S. Pat. No. 3,627,469. An ink composition has been prepared as a telltale for ethylene oxide sterilization which utilizes the fact that MgCl.sub.2 reacts with ethylene oxide to produce Mg(OH).sub.2 which is detected by a pH sensitive dye; see U.S. Pat. No. 3,098,751. This same mechanism has been used to prepare a physical sterilization indicator by depositing the reactants on an absorbent material and enclosing the composition in a sealed envelope of gas permeable film such as polyethylene; see Royce and Bower "An Indicator Control Device for Ethylene Oxide Sterilization." J. Pharm. and Pharm. 11, Suppl. 294T-298T.
Recently, a device has been developed which integrates the time-temperature history of a process by presenting a color change which moves along a wick in response to the presence of an acidic or basic gaseous atmosphere; see U.S. Pat. Nos. 3,946,611 and 3,932,134.